SWAP-70は,膜ラフリングのシグナル伝達を媒介するグアニン-ヌクレオチド交換因子です
Masahiro Shinohara1, Yoh Terada, Akihiro Iwamatsu
1Department of Applied Biological Chemistry, Faculty of Agricultural and Life Science, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.
Nature
|April 19, 2002
まとめ
SWAP-70は,フォスファディチルイノシトール-3,4,5-トリスホスファート (PtdIns(3,4,5) P3) を結合する新しいラック-グアニン核酸代謝因子 (GEF) として特定されています. このタンパク質は,Ras信号伝達とは独立して,成長因子誘発の細胞膜乱れとRac活性化を媒介する.
科学分野:
- 細胞信号伝達と分子生物学
- リピドの第2のメッセンジャー経路
- 細胞骨格のダイナミクス
背景:
- フォスフォヒノシチド-3-OHキナーゼ (PI(3) K) は,重要な脂質第2メッセンジャーであるフォスファディチリノシトール-3,4,5-トリスホスファート (PtdIns(3,4,5) P3) を生成する.
- PtdIns ((3,4,5) P3は,活性化,生存,細胞骨格の再編成を含む重要な細胞プロセスを調節する.
- PtdIns ((3,4,5) P3のターゲットとその機能の完全なセットは,まだ完全に理解されていません.
研究 の 目的:
- フォスファディチルイノシトール-3,4,5-トリスホスファート (PtdIns(3,4,5) P3) の新しい標的を特定する.
- 信号伝達経路におけるSWAP-70の役割を調査する.
- SWAP-70が細胞膜ダイナミクスとRacの活性化を調節するメカニズムを解明する.
主な方法:
- SWAP-70がPtdInsと固有の結合を証明した ((3,4,5) P3.3.
- 成長因子刺激 (EGF,PDGF) を用いて,SWAP-70の局所化と膜乱れを観察した.
- PtdIns ((3,4,5) P3を結合する機能的必要性を評価する能力が欠けている変異体SWAP-70が採用されました.
- Rac. 上のSWAP-70のグアニンヌクレオチド交換活動を評価しました.
- SWAP-70欠乏した線維芽細胞を研究し,Racの活性化と膜の乱れにおけるその役割を確認した.
主要な成果:
- SWAP-70は,特に,フォスファディチルイノシトール-3,4,5-トリフォスファート (PtdIns(3,4,5) P3) に結合する.
- 成長因子刺激は,PI(3) Kに依存した方法で,SWAP-70の細胞膜ラッフルへの転移を誘導する.
- 変異したSWAP-70はPtdInsを結合することができない.
- SWAP-70は,Rac-グアニンヌクレオチド交換因子 (GEF) として作用し,Rac.のPtdIns{3,4,5) P3-依存のヌクレオチド交換を触媒化する.
- SWAP-70欠乏した線維芽細胞は,EGF刺激で膜のラッフリングが低下し,Racの活性化が低下した.
結論:
- SWAP-70は,PtdIns ((3,4,5) P3をRacの活性化に直接リンクする新しいタイプのRac-GEFです.
- SWAP-70はチロシンキナーゼ受容体からRacへの信号を媒介し,Rasから独立して膜ラフリングを制御します.
- この研究では,SWAP-70が細胞形態学と成長因子への反応を調節する新しいシグナル伝達軸を明らかにしています.
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